Cardiotonic agents such as 4,5-dihydro-6-(substituted)-phenyl-3(2H)-pyridazinone are described in U.S. Pat. No. 4,353,905. Cardiotonic agents such as 1,2-dihydro-5-(substituted)-phenyl]-2-oxo-3-pyridinecarbonitriles are described in U.S. application Ser. No. 515,799 of July 22, 1983. Other cardiotonic agents have been reported in U.S. Pat. No. 4,004,012 and 4,313,951.
Antihypertensive agents which attribute their activity to inhibition of angiotensin-converting enzyme (ACE inhibitors) have been described. For example, aryl derivatives of 1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acids are described in U.S. Pat. No. 4,344,949 and acylated octahydro-1H-indole-2-carboxylic acids are described in U.S. Pat. No. 4,425,355.
Combinations of antihypertensive agents and diuretics are well-known in the art. ACE-inhibiting antihypertensive agents have also been reported to be useful in combination with diuretic compounds in U.S. Pat. No. 4,217,347. Combinations of ACE inhibitors with diuretics, saluretics, .alpha.-adrenolytics, .beta.-blockers, calcium antagonists or vascular dopaminergic receptor agonists are reported in European Patent Publications 51,020, 69,846, and 49,658.
The present invention relates to a combination of certain ACE-inhibitors with certain cardiotonic agents resulting in a synergistic increase in myocardial contractility and cardiac output thereby rendering such combinations useful in treating heart failure.